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HnRNPL inhibits the osteogenic differentiation of PDLCs stimulated by SrCl2 through repressing Setd2

Xiaoshi Jia1, Richard J Miron2, Chengcheng Yin1

  • 1The State Key Laboratory Breeding Base of Basic Science of Stomatology (Hubei-MOST) & Key Laboratory of Oral Biomedicine Ministry of Education, Wuhan University, Wuhan, People's Republic of China.

Journal of Cellular and Molecular Medicine
|February 13, 2019
PubMed

Insights

Strontium (Sr) ions promote bone regeneration in periodontitis by influencing the splicing factor hnRNPL in periodontal ligament stem cells (PDLCs). This epigenetic mechanism, involving hnRNPL and Setd2, offers insights for treating combined periodontitis and osteoporosis.

Area of Science:

  • Biomaterials Science
  • Stem Cell Biology
  • Epigenetics

Background:

  • Periodontitis and osteoporosis share risk factors and exacerbate bone loss.
  • Strontium Ranelate and strontium-substituted mesoporous bioactive glass (Sr-MBG) show potential in managing these conditions.
  • Sr ion stimulation down-regulates heterogeneous nuclear ribonucleoprotein L (hnRNPL) in periodontal ligament stem cells (PDLCs) via AKT pathway activation.

Purpose of the Study:

  • To investigate the mechanism of strontium-stimulated periodontal regeneration.
  • To elucidate the role of the splicing factor hnRNPL in strontium-induced osteogenesis of PDLCs.
  • To explore the interplay between hnRNPL and Setd2 in the context of periodontitis and osteoporosis.

Main Methods:

  • Cell culture of PDLCs.
  • Stimulation with Strontium Chloride (SrCl2).
  • Analysis of hnRNPL and Setd2 expression and function.
  • Assessment of osteogenic differentiation markers.

Main Results:

  • Strontium chloride (SrCl2) stimulation of PDLCs involves the epigenetic mechanism of splicing factor hnRNPL in osteogenesis.
  • hnRNPL restrains osteogenic differentiation by down-regulating the H3K36me3-specific methyltransferase Setd2.
  • Sr stimulation leads to decreased hnRNPL levels, promoting osteogenesis.

Conclusions:

  • The epigenetic regulation by hnRNPL is crucial for strontium-mediated osteogenesis in PDLCs.
  • The distinct roles of hnRNPL and Setd2 suggest potential therapeutic strategies for periodontitis patients with co-existing osteoporosis.
  • Sr-MBG scaffolds show promise for periodontal regeneration, with strontium ions playing a key role in the underlying molecular mechanisms.
Keywords:
RNA splicingbioengineeringhnRNPLosteoporosisperiodontal ligament stem cells

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